The “urothelial cancer” is a collective name for bladder cancer, renal pelvis cancer, urinary duct cancer, and the like. Such cancers are caused by canceration of a transitional epithelium cell of the urinary tract, and their properties are considered to be common or shared. The number of patients suffered from urothelial cancer is the second-highest among patients with urogenital cancers, following prostate cancer. According to the “Population Survey Report” provided in 2001 by the Statistics and Information Department at the Ministry of Health, Labour and Welfare of Japan, the number of patients with bladder cancer was as many as 9,765 for males and 3,243 for females, and the number of patients died of bladder cancer was 3,459 for males and 1,587 for females, annually in Japan. By contrast, the number of patients with renal pelvis cancer or urinary duct cancer is considerably smaller than those with bladder cancer, and the numbers of patients died of these cancers were 797 and 713, respectively, in total of males and females.
Although there are no studies on prevention of bladder cancer or any other urothelial cancer, the development of bladder cancer is often found in people in their 50's or older, and men are more likely to develop such cancer, at a rate 2 to 3 times higher than that for women. Also, smokers are approximately 4 times higher in the onset of bladder cancer than nonsmokers. Bladder cancer is roughly classified into two types: i.e., superficial bladder cancer and infiltrative bladder cancer. Superficial papillary tumors have relatively low malignancy and protrudes on the inner cavity of the bladder (i.e., the inner surface of the bladder), but the degree of infiltration is shallow, and the surface is papilliform (like a cauliflower) with thin stems. Such cancer can be treated endoscopically; however, it recurs in the bladders of half or more patients. The depth of cancer invasion may reach the submucosal level, although it would not reach the bladder's muscle layer. In contrast, infiltrative cancer is high in malignancy, the degree of invasion is deep, it tends to invade the deep portion of the bladder wall, and it may metastasize to other portions of the body. In order to treat infiltrative cancer, accordingly, treatment that imposes a burden on a patient's body, such as bladder extirpation, use of an anticancer agent, or radiation therapy, is required.
The most common symptom of bladder cancer is painless hematuria; however, the symptoms may be similar to those of cystitis, such as increased urinary frequency, pain during urination, or the feeling of incomplete emptying of the bladder. Diagnosis of bladder cancer is carried out via, for example, urine analysis (cytological diagnosis), X-ray photography, or endoscopic diagnosis. Due to a lack of specific and highly sensitive tumor markers that can be used for the blood or urine useful for early diagnosis, however, bladder cancer is often detected after the cancer has progressed. Urothelial cancer that develops at sites other than the bladder also has the same properties. Accordingly, practical application of a simple detection method with the use of specific and highly sensitive tumor markers for urothelial cancer, and particularly for bladder cancer, is desired.
A variety of markers and methods have been proposed for detection and determination of bladder cancer. Examples thereof include methods wherein bladder cancer is evaluated based on changes in expression levels of genes such as nucleophosmin/B23 (JP Patent Publication (kokai) No. 2004-337120 (A)), HURP (JP Patent Publication (kokai) No. 2004-248508 (A)), or CYP4B1 or CYP4B2 (JP Patent Publication (kokai) No. 2002-238599 (A)); a method wherein bladder cancer is evaluated based on the expression or amount of a given protein in a urine specimen (JP Patent Publication (kokai) Nos. 2004-61288 (A) and H7-309895 (1995)(A)); and a method wherein bladder cancer is evaluated using the concentration of soluble Fas in the blood as an indication (JP Patent Publication (kokai) No. 2000-131321 (A)).